Project Summary/Abstract Physical Sciences Inc. (PSI), in collaboration with the Department of Pathology at the Massachusetts General Hospital (MGH) and the Divisions of Pulmonary and Critical Care Medicine at MGH and Beth Israel Lahey Health (BILH), proposes to develop and evaluate a novel technology for assessing pulmonary fibrosis, which is a respiratory disease leading to serious breathing problems. This disease consists of the accumulation of excess fibrous connective tissue within the lungs (this process is called fibrosis), leading to thickening of the walls of the bronchioles, and thus causes reduced oxygen supply in the blood. As a consequence patients suffer from perpetual shortness of breath. Pulmonary fibrosis is usually diagnosed during regular doctor office visits, by listening with the stethoscope, and confirmed with X-rays and CT scanning. However, since misdiagnosis is common, biopsy is ultimately performed to confirm findings. Unfortunately, large pieces of tissue are needed to evaluate the presence of fibrosis. Therefore, video assisted thoracoscopic wedge biopsy (VATS) is used for this purpose. This procedure has multiple side effects, including inflammation, tissue morbidity, and severe bleeding. Furthermore, since it requires tissue processing and pathologic interpretation, the procedure becomes expensive, while the results are not immediately available. PSI's proposed alternative approach to regular VATS wedge resections is to investigate tissue morphology and mechanical properties in situ by using a minimally invasive needle-type smart optical probe, which eliminates the need to remove any tissue. Furthermore, the results are immediately available during biopsy. This technology will be first tested In Phase I in a Bleomycin-induced pulmonary fibrosis rat model to determine its efficacy for reliable diagnosis. Based on Phase I findings, the technology will be further improved during Phase II and its efficacy will be further tested in human patients at MGH and BILH. Successful development and demonstration of the proposed PSI technology will enable reliable improved diagnosis at lower costs while eliminating side effects associated to the regular biopsy.